Patent GB-804987-A (GB)
Title: Oxazolines
IPC: C07D263/14
Filed: 1956-05-29
Abstract: The invention comprises: (a) oxazolines of the general formul : <FORM:0804987/IV (b)/1> (and in some cases mixtures thereof), wherein R represents hydrogen or an acyl group and X hydrogen or a nitro group; (b) a mixture of D - threo - 2 - a  - azidoethyl - 5 - p - nitrophenyl-4 - hydroxymethyloxazoline and D - threo - 2 - a  - azidoethyl - 4 - p - nitrophehylhydroxymethyloxazoline (containing the group <FORM:0804987/IV (b)/2> in the formul  above); (c) production of compounds (a) by the processes of Examples (1)-(8), (10) and (11) below, which are described in general terms as follows: (i) reaction of azidoalkanonitriles with the free 2-aminopropane-1 : 3-diols (if desired in an anhydrous solvent); (ii) reaction of azidoacylimino-ethers or -thioethers with the 2-aminopropane-1 : 3-diols or a derivative thereof modified in the 1- or 3-position, one or other of the reactants being in the form of a salt; these reactions may be carried out in water, organic solvents or weak bases, and when a derivative of the propanediol is used (to obtain a single product instead of a mixture corresponding to the two formul above), the substituent on the one hydroxy group may be subsequently split off; (iii) the action of an agent splitting off water (e.g. thionyl chloride, p-toluenesulphonyl chloride or conc. H2SO4) on 1-phenyl- or 1-p-nitrophenyl - 2 - azidoacylamino - 1 : 3 - propanediols or their derivatives modified in the 1- or 3-position; (iv) for compounds in which X is NO2, nitrating those in which X is H and in which preferably the hydroxy group is protected; (v) subjecting oxazoline esters, obtained by reacting p-nitrophenylserine esters with azidoacylimino ethers, to selective reduction (e.g. with an alkali metal or alkali metal-boron hydride); (vi) alkaline hydrolysis of 2-azidomethyl - 5 - aryl - 4 - chloromethyloxazolines obtained by reacting 1-aryl-2-azidoacetylamino-1 : 3-dichloropropanes with sodium hydroxide.  In examples: (1) to (5) D-(-)-threo-p-nitrophenyl - 2 - aminopropane - 1 : 3 - diol is reacted with azodoacetiminoethyl ether hydrochloride in pyridine, methanol ethanol or water, or with azidoacetiminomethyl ether hydrochloride in pyridine; (6) and (8) DL-threo-1-p-nitrophenyl- and -1-phenyl-2-aminopropane-1 : 3-diol are reacted with azidoacetiminoethyl ether hydrochloride in water; (7) D - (+) - threo - 1 - p - nitrophenyl - 2 - azidoacetylamino - 3 - benzoyloxypropan - 1 - ol is reacted with thionyl chloride; (9) D-(-)-threo-1 - p - nitropheny - 2 - aminopropane - 1 : 3 - diol is reacted with a -azidopropioniminomethyl ether hydrochloride in pyridine to produce the mixture defined in (b) above; (10) D-(-)-threo-1 - p - nitrophenyl - 2 - azidoacetylamino - 1 : 3-dichloropropane is treated with aqueous alcoholic caustic soda, and the resulting D-threo-2-azidomethyl - 5 - p - nitrophenyl - 4 - chloromethyloxazoline is converted to the 4-hydroxymethyl compound by alkaline hydrolysis; (11) DL - threo - 2 - azidomethyl - 5 - p - nitrophenyl-oxazoline-4-carboxylic acid ethyl ester is reduced with sodium borohydride and calcium iodide in tetrahydrofuran.  Starting materials.  Azidoacylimino ethers are obtained (as hydrohalides) by the action of a hydrogen halide (e.g. HCl) on a mixture of an azidoalkanonitrile (e.g. azidoacetonitrile or azidopropionitrile) and an alcohol (e.g. ethanol or methanol). DL-threo-2-Azidomethyl-5-p-nitrophenyloxazoline-4-carboxylic acid ethyl ester is prepared by reacting p-nitrophenylserine ethyl ester with azidoacetiminoether hydrochloride in alcohol. Specification 804,986 is referred to.